Circulating Cytokines Reflect Mucosal Inflammatory Status in Patients with Crohn's Disease

There is a great need for a simple activity assessment tool that can reliably predict activity in patients with Crohn's disease (CD). To investigate the relationship between serum cytokines and endoscopic activity of CD using Crohn's Disease Endoscopic Index of Severity (CDEIS) as a gold standard. We prospectively evaluated 32 firmly established CD patients using ileocolonoscopy, CDEIS score, and Crohn's Disease Activity Index (CDAI) score. Blood samples for cytokine analysis were obtained 1 day prior to procedure. The correlation between CDEIS and CDAI was moderate (r = 0.43; P = 0.01); however, the correlation between CDEIS and inflammatory cytokines was excellent, with the highest coefficients for tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) (r = 0.96 and r = 0.96, respectively; P < 0.001). CDEIS and anti-inflammatory cytokines were correlated nonlinearly (power function). We identified two separate models for predicting CDEIS value, based on the best performing pro-inflammatory [CDEIS = 0.445 x (IL-6) - 5,143] and anti-inflammatory [CDEIS = 27.478 x (IL-10)(-0.71)] cytokines. Both IL-6 and IL-10 models had high adjusted R (2) values (0.916 and 0.954, respectively). IL-6 had excellent diagnostic accuracy for detecting patients with CDEIS > 7 (active disease), with area under the receiver operating characteristic (ROC) curve of 1.0 [95% confidence interval (CI) = 0.89-1.0; P < 0.001]. Serum cytokine levels are excellent predictors of endoscopic activity in patients with CD.